Skip to main content
Top
Published in: European Journal of Nutrition 2/2020

01-03-2020 | Alkaloids | Original Contribution

Identification of potential human urinary biomarkers for tomato juice intake by mass spectrometry-based metabolomics

Authors: Yannick Hövelmann, Annika Jagels, Robin Schmid, Florian Hübner, Hans-Ulrich Humpf

Published in: European Journal of Nutrition | Issue 2/2020

Login to get access

Abstract

Purpose

Dietary biomarkers allow the accurate and objective determination of the dietary intake of humans and can thus be valuable for investigating the relation between consumption of foods and biochemical as well as physiological responses. The objective of this study was the identification of potential urinary biomarkers for consumption of tomato juice.

Methods

In the course of a dietary intervention study, the human urine metabolome of a study cohort was compared between a tomato-free diet and after intake of tomato juice by application of an LC-HRMS-based metabolomics approach. The data acquisition was achieved using an orbitrap mass spectrometer, followed by multistage data processing and univariate as well as multivariate statistical analysis to identify discriminating features.

Results

Statistical analysis revealed several unique features detectable after tomato juice intake. The most discriminating markers were putatively identified as hydroxylated and sulfonated metabolites of esculeogenin B, aglycone of the steroidal glycoalkaloid esculeoside B recently found in tomato juice. Furthermore, the β-carboline alkaloids tangutorid E and F and glucuronidated derivatives thereof were identified in urine.

Conclusions

Steroidal glycoalkaloids in tomato juice are cleaved after ingestion, and hydroxylated and sulfonated metabolites of their aglycones might serve as urinary biomarkers for tomato juice intake. Similarly, β-carboline alkaloids and glucuronidated derivatives were identified as potential urinary biomarkers. Both the aglycones of the steroidal alkaloids and the β-carboline alkaloids might exhibit biological activities worth investigating.
Appendix
Available only for authorised users
Literature
1.
go back to reference Thompson FE, Subar AF, Loria CM, Reedy JL, Baranowski T (2010) Need for technological innovation in dietary assessment. J Acad Nutr Diet 110:48–51 Thompson FE, Subar AF, Loria CM, Reedy JL, Baranowski T (2010) Need for technological innovation in dietary assessment. J Acad Nutr Diet 110:48–51
2.
go back to reference Bingham SA (2002) Biomarkers in nutritional epidemiology. Public Health Nutr 5:821–827PubMed Bingham SA (2002) Biomarkers in nutritional epidemiology. Public Health Nutr 5:821–827PubMed
3.
go back to reference McCabe-Sellers B (2010) Advancing the art and science of dietary assessment through technology. J Am Diet Assoc 110:52–54PubMed McCabe-Sellers B (2010) Advancing the art and science of dietary assessment through technology. J Am Diet Assoc 110:52–54PubMed
4.
go back to reference Hedrick VE, Dietrich AM, Estabrooks PA, Savla J, Serrano E, Davy BM (2012) Dietary biomarkers: advances, limitations and future directions. Nutr J 11:109PubMedPubMedCentral Hedrick VE, Dietrich AM, Estabrooks PA, Savla J, Serrano E, Davy BM (2012) Dietary biomarkers: advances, limitations and future directions. Nutr J 11:109PubMedPubMedCentral
5.
go back to reference Wishart DS (2008) Metabolomics: application to food science and nutrition research. Trends Food Sci Technol 19:482–493 Wishart DS (2008) Metabolomics: application to food science and nutrition research. Trends Food Sci Technol 19:482–493
6.
go back to reference Heinzmann SS, Brown IJ, Chan Q, Bictash M, Dumas ME, Kochhar S et al (2010) Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. Am J Clin Nutr 92:436–443PubMedPubMedCentral Heinzmann SS, Brown IJ, Chan Q, Bictash M, Dumas ME, Kochhar S et al (2010) Metabolic profiling strategy for discovery of nutritional biomarkers: proline betaine as a marker of citrus consumption. Am J Clin Nutr 92:436–443PubMedPubMedCentral
7.
go back to reference Lloyd AJ, Beckmann M, Fave G, Mathers JC, Draper J (2011) Proline betaine and its biotransformation products in fasting urine samples are potential biomarkers of habitual citrus fruit consumption. Br J Nutr 106:812–824PubMed Lloyd AJ, Beckmann M, Fave G, Mathers JC, Draper J (2011) Proline betaine and its biotransformation products in fasting urine samples are potential biomarkers of habitual citrus fruit consumption. Br J Nutr 106:812–824PubMed
8.
go back to reference Lang R, Lang T, Bader M, Beusch A, Schlagbauer V, Hofmann T (2017) High-throughput quantitation of proline betaine in foods and suitability as a valid biomarker for citrus consumption. J Agric Food Chem 65:1613–1619PubMed Lang R, Lang T, Bader M, Beusch A, Schlagbauer V, Hofmann T (2017) High-throughput quantitation of proline betaine in foods and suitability as a valid biomarker for citrus consumption. J Agric Food Chem 65:1613–1619PubMed
9.
go back to reference Mennen LI, Sapinho D, Ito H, Bertrais S, Galan P, Hercberg S et al (2006) Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods. Br J Nutr 96:191–198PubMed Mennen LI, Sapinho D, Ito H, Bertrais S, Galan P, Hercberg S et al (2006) Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods. Br J Nutr 96:191–198PubMed
10.
go back to reference Saenger T, Hübner F, Humpf HU (2017) Short-term biomarkers of apple consumption. Mol Nutr Food Res 61:1600629 Saenger T, Hübner F, Humpf HU (2017) Short-term biomarkers of apple consumption. Mol Nutr Food Res 61:1600629
11.
go back to reference Ito H, Gonthier MP, Manach C, Morand C, Mennen L, Rémésy C et al (2005) Polyphenol levels in human urine after intake of six different polyphenol-rich beverages. Br J Nutr 94:500–509PubMed Ito H, Gonthier MP, Manach C, Morand C, Mennen L, Rémésy C et al (2005) Polyphenol levels in human urine after intake of six different polyphenol-rich beverages. Br J Nutr 94:500–509PubMed
12.
go back to reference Llorach R, Urpi-Sarda M, Jauregui O, Monagas M, Andres-Lacueva C (2009) An LC-MS-based metabolomics approach for exploring urinary metabolome modifications after cocoa consumption. J Proteom Res 8:5060–5068 Llorach R, Urpi-Sarda M, Jauregui O, Monagas M, Andres-Lacueva C (2009) An LC-MS-based metabolomics approach for exploring urinary metabolome modifications after cocoa consumption. J Proteom Res 8:5060–5068
13.
go back to reference Canene-Adams K, Campbell JK, Zaripheh S, Jeffery EH, Erdman JW (2005) The tomato as a functional food. J Nutr 135:1226–1230PubMed Canene-Adams K, Campbell JK, Zaripheh S, Jeffery EH, Erdman JW (2005) The tomato as a functional food. J Nutr 135:1226–1230PubMed
14.
go back to reference Ghavipour M, Saedisomeolia A, Djalali M, Sotuodeh G, Eshraghyan MR, Moghadam AM et al (2013) Tomato juice consumption reduces systemic inflammation in overweight and obese females. Br J Nutr 109:2031–2035PubMed Ghavipour M, Saedisomeolia A, Djalali M, Sotuodeh G, Eshraghyan MR, Moghadam AM et al (2013) Tomato juice consumption reduces systemic inflammation in overweight and obese females. Br J Nutr 109:2031–2035PubMed
15.
go back to reference Ghavipour M, Sotoudeh G, Ghorbani M (2015) Tomato juice consumption improves blood antioxidative biomarkers in overweight and obese females. Clin Nutr 34:805–809PubMed Ghavipour M, Sotoudeh G, Ghorbani M (2015) Tomato juice consumption improves blood antioxidative biomarkers in overweight and obese females. Clin Nutr 34:805–809PubMed
16.
go back to reference Silaste ML, Alfthan G, Aro A, Kesäniemi YA, Hörkkö S (2007) Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation. Br J Nutr 98:1251–1258PubMed Silaste ML, Alfthan G, Aro A, Kesäniemi YA, Hörkkö S (2007) Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation. Br J Nutr 98:1251–1258PubMed
17.
go back to reference Moco S, Bino RJ, Vorst O, Verhoeven HA, de Groot J, van Beek TA et al (2006) A liquid chromatography-mass spectrometry-based metabolome database for tomato. Plant Physiol 141:1205–1218PubMedPubMedCentral Moco S, Bino RJ, Vorst O, Verhoeven HA, de Groot J, van Beek TA et al (2006) A liquid chromatography-mass spectrometry-based metabolome database for tomato. Plant Physiol 141:1205–1218PubMedPubMedCentral
18.
go back to reference Iijima Y, Watanabe B, Sasaki R, Takenaka M, Ono H, Sakurai N et al (2013) Steroidal glycoalkaloid profiling and structures of glycoalkaloids in wild tomato fruit. Phytochem 95:145–157 Iijima Y, Watanabe B, Sasaki R, Takenaka M, Ono H, Sakurai N et al (2013) Steroidal glycoalkaloid profiling and structures of glycoalkaloids in wild tomato fruit. Phytochem 95:145–157
19.
go back to reference Nohara T, Fujiwara Y, Zhou JR, Urata J, Ikeda T, Murakami K et al (2015) Saponins, esculeosides B-1 and B-2, in tomato juice and sapogenol, esculeogenin B1. Chem Pharm Bull 63:848–850PubMed Nohara T, Fujiwara Y, Zhou JR, Urata J, Ikeda T, Murakami K et al (2015) Saponins, esculeosides B-1 and B-2, in tomato juice and sapogenol, esculeogenin B1. Chem Pharm Bull 63:848–850PubMed
20.
go back to reference Cichon MJ, Riedl KM, Wan L, Thomas-Ahner JM, Francis DM, Clinton SK et al (2017) Plasma metabolomics reveals steroidal alkaloids as novel biomarkers of tomato intake in mice. Mol Nutr Food Res 61:1700241 Cichon MJ, Riedl KM, Wan L, Thomas-Ahner JM, Francis DM, Clinton SK et al (2017) Plasma metabolomics reveals steroidal alkaloids as novel biomarkers of tomato intake in mice. Mol Nutr Food Res 61:1700241
21.
go back to reference Gika HG, Theodoridis GA, Plumb RS, Wilson ID (2014) Current practice of liquid chromatography-mass spectrometry in metabolomics and metabonomics. J Pharm Biomed Anal 87:12–25PubMed Gika HG, Theodoridis GA, Plumb RS, Wilson ID (2014) Current practice of liquid chromatography-mass spectrometry in metabolomics and metabonomics. J Pharm Biomed Anal 87:12–25PubMed
22.
go back to reference Werner E, Heilier JF, Ducruix C, Ezan E, Junot C, Tabet JC (2008) Mass spectrometry for the identification of the discriminating signals from metabolomics: current status and future trends. J Chromatogr 871:143–163 Werner E, Heilier JF, Ducruix C, Ezan E, Junot C, Tabet JC (2008) Mass spectrometry for the identification of the discriminating signals from metabolomics: current status and future trends. J Chromatogr 871:143–163
23.
go back to reference Chambers MC, MacLean B, Burke R, Amode D, Ruderman DL, Neumann S et al (2012) A cross-platform toolkit for mass spectrometry and proteomics. Nat Biotechnol 30:918–920PubMedPubMedCentral Chambers MC, MacLean B, Burke R, Amode D, Ruderman DL, Neumann S et al (2012) A cross-platform toolkit for mass spectrometry and proteomics. Nat Biotechnol 30:918–920PubMedPubMedCentral
24.
go back to reference Pluskal T, Castillo S, Villar-Briones A, Oresic M (2010) MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinform 11:395 Pluskal T, Castillo S, Villar-Briones A, Oresic M (2010) MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data. BMC Bioinform 11:395
25.
go back to reference Xia J, Wishart DS (2016) Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis. Curr Protoc Bioinform 55:14.10.1–14.10.91 Xia J, Wishart DS (2016) Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis. Curr Protoc Bioinform 55:14.10.1–14.10.91
26.
go back to reference Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vazquez-Fresno R et al (2018) HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res 46:D608–D617PubMed Wishart DS, Feunang YD, Marcu A, Guo AC, Liang K, Vazquez-Fresno R et al (2018) HMDB 4.0: the human metabolome database for 2018. Nucleic Acids Res 46:D608–D617PubMed
27.
go back to reference Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR et al (2005) METLIN: a metabolite mass spectral database. Ther Drug Monit 27:747–751PubMed Smith CA, O’Maille G, Want EJ, Qin C, Trauger SA, Brandon TR et al (2005) METLIN: a metabolite mass spectral database. Ther Drug Monit 27:747–751PubMed
28.
go back to reference Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA et al (2007) Proposed minimum reporting standards for chemical analysis. Metabolomics 3:211–221PubMedPubMedCentral Sumner LW, Amberg A, Barrett D, Beale MH, Beger R, Daykin CA et al (2007) Proposed minimum reporting standards for chemical analysis. Metabolomics 3:211–221PubMedPubMedCentral
29.
go back to reference Diem S, Herderich M (2001) Reaction of tryptophan with carbohydrates: identification and quantitative determination of novel β-carboline alkaloids in food. J Agric Food Chem 49:2486–2492PubMed Diem S, Herderich M (2001) Reaction of tryptophan with carbohydrates: identification and quantitative determination of novel β-carboline alkaloids in food. J Agric Food Chem 49:2486–2492PubMed
30.
go back to reference Zhao JQ, Wang YM, Yang YL, Zeng Y, Wang QL, Shao Y et al (2017) Isolation and identification of antioxidant and α-glucosidase inhibitory compounds from fruit juice of Nitraria tangutorum. Food Chem 227:93–101PubMed Zhao JQ, Wang YM, Yang YL, Zeng Y, Wang QL, Shao Y et al (2017) Isolation and identification of antioxidant and α-glucosidase inhibitory compounds from fruit juice of Nitraria tangutorum. Food Chem 227:93–101PubMed
31.
go back to reference Caprioli G, Cahill M, Logrippo S, James K (2015) Elucidation of the mass fragmentation pathways of tomatidine and β1-hydroxytomatine using orbitrap-mass spectrometry. Nat Prod Commun 10:575–576PubMed Caprioli G, Cahill M, Logrippo S, James K (2015) Elucidation of the mass fragmentation pathways of tomatidine and β1-hydroxytomatine using orbitrap-mass spectrometry. Nat Prod Commun 10:575–576PubMed
32.
go back to reference Levsen K, Schiebel HM, Behnke B, Dötzer R, Dreher W, Elend M (2005) Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview. J Chromatogr A 1067:55–72PubMed Levsen K, Schiebel HM, Behnke B, Dötzer R, Dreher W, Elend M (2005) Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview. J Chromatogr A 1067:55–72PubMed
33.
go back to reference Strott CA (2002) Sulfonation and molecular action. Endocr Rev 23:703–732PubMed Strott CA (2002) Sulfonation and molecular action. Endocr Rev 23:703–732PubMed
34.
go back to reference Leowattana W (2004) DHEAS as a new diagnostic tool. Clin Chim Acta 341:1–15PubMed Leowattana W (2004) DHEAS as a new diagnostic tool. Clin Chim Acta 341:1–15PubMed
35.
go back to reference Fujiwara Y, Takaki A, Uehara Y, Ikeda T, Okawa M, Yamauchi K et al (2004) Tomato steroidal alkaloid glycosides, esculeosides A and B, from ripe fruits. Tetrahedron 60:4915–4920 Fujiwara Y, Takaki A, Uehara Y, Ikeda T, Okawa M, Yamauchi K et al (2004) Tomato steroidal alkaloid glycosides, esculeosides A and B, from ripe fruits. Tetrahedron 60:4915–4920
36.
go back to reference Manabe H, Fujiwara Y, Ikeda T, Ono M, Murakami K, Zhou JR et al (2013) Saponins esculeosides B-1 and B-2 in Italian canned tomatoes. Chem Pharm Bull 61:764–767PubMed Manabe H, Fujiwara Y, Ikeda T, Ono M, Murakami K, Zhou JR et al (2013) Saponins esculeosides B-1 and B-2 in Italian canned tomatoes. Chem Pharm Bull 61:764–767PubMed
37.
go back to reference Friedman M (2002) Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem 50:5751–5780PubMed Friedman M (2002) Tomato glycoalkaloids: role in the plant and in the diet. J Agric Food Chem 50:5751–5780PubMed
38.
go back to reference Nohara T, Ono M, Ikeda T, Fujiwara Y, El-Aasr M (2010) The tomato saponin, esculeoside A. J Nat Prod 73:1734–1741PubMed Nohara T, Ono M, Ikeda T, Fujiwara Y, El-Aasr M (2010) The tomato saponin, esculeoside A. J Nat Prod 73:1734–1741PubMed
39.
go back to reference Fujiwara Y, Kiyota N, Hori M, Matsushita S, Iijima Y, Aoki K et al. Arterioscler (2007) Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. Thromb Vasc Biol 27:2400–2406 Fujiwara Y, Kiyota N, Hori M, Matsushita S, Iijima Y, Aoki K et al. Arterioscler (2007) Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. Thromb Vasc Biol 27:2400–2406
40.
go back to reference Fujiwara Y, Kiyota N, Tsurushima K, Yoshitomi M, Horlad H, Ikeda T et al (2012) Tomatidine, a tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting Acyl-CoA:cholesterol Acyl-transferase (ACAT). J Agric Food Chem 60:2472–2479PubMed Fujiwara Y, Kiyota N, Tsurushima K, Yoshitomi M, Horlad H, Ikeda T et al (2012) Tomatidine, a tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting Acyl-CoA:cholesterol Acyl-transferase (ACAT). J Agric Food Chem 60:2472–2479PubMed
41.
go back to reference Allen JRF, Holmstedt BR (1980) The simple β-carboline alkaloids. Phytochem 19:1573–1582 Allen JRF, Holmstedt BR (1980) The simple β-carboline alkaloids. Phytochem 19:1573–1582
42.
go back to reference Adachi J, Mizoi Y, Naito T, Ogawa Y, Uetani Y, Ninomiya I (1991) Identification of tetrahydro-β-carboline-3-carboxylic acid in foodstuffs, human urine and human milk. J Nutr 121:646–652PubMed Adachi J, Mizoi Y, Naito T, Ogawa Y, Uetani Y, Ninomiya I (1991) Identification of tetrahydro-β-carboline-3-carboxylic acid in foodstuffs, human urine and human milk. J Nutr 121:646–652PubMed
43.
go back to reference Herraiz T, Galisteo J (2002) Identification and occurrence of the novel alkaloid pentahydroxypentyl-tetrahydro-β-carboline-3-carboxylic acid as a tryptophan glycoconjugate in fruit juices and jams. J Agric Food Chem 50:4690–4695PubMed Herraiz T, Galisteo J (2002) Identification and occurrence of the novel alkaloid pentahydroxypentyl-tetrahydro-β-carboline-3-carboxylic acid as a tryptophan glycoconjugate in fruit juices and jams. J Agric Food Chem 50:4690–4695PubMed
44.
go back to reference Cao R, Peng W, Wang Z, Xu A (2007) β-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem 14:479–500PubMed Cao R, Peng W, Wang Z, Xu A (2007) β-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem 14:479–500PubMed
45.
go back to reference Khan H, Patel S, Kamal MA (2017) Pharmacological and toxicological profile of harmane-β-carboline alkaloid: friend or foe. Curr Drug Metab 18:853–857PubMed Khan H, Patel S, Kamal MA (2017) Pharmacological and toxicological profile of harmane-β-carboline alkaloid: friend or foe. Curr Drug Metab 18:853–857PubMed
Metadata
Title
Identification of potential human urinary biomarkers for tomato juice intake by mass spectrometry-based metabolomics
Authors
Yannick Hövelmann
Annika Jagels
Robin Schmid
Florian Hübner
Hans-Ulrich Humpf
Publication date
01-03-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 2/2020
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-019-01935-4

Other articles of this Issue 2/2020

European Journal of Nutrition 2/2020 Go to the issue